The Danish Familial Hypercholesterolemia Organized Coronary Screening Trial

NCT05758779 | Active Not Recruiting

• 1 other identifier: DANFOCOS
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Familial hypercholesterolemia (FH) is the most common inherited cause of atherosclerotic cardiovascular disease (ASCVD) with a prevalence of approximately one in 200 individuals, however only few of the estimated 30.000 patients with FH in Denmark has been diagnosed. FH is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and a high risk of premature ASCVD in particular coronary artery disease. The presence of atherosclerosis measured by cardiac computed tomography (CT) is a reliable predictor of future cardiovascular events and may help guide clinicians with regard to the lifestyle modifying therapies and lipid-lowering treatment. However, the prevalence and degree of coronary atherosclerosis in Danish FH patients without symptoms of ASCVD is unknown. Therefore, the invetigators aimed to:

• Screen FH patients in a Danish setting for subclinical coronary atherosclerosis to improve lipid-lowering treatment and,
• Test if coronary CT screening can help to reach LDL-C therapy goals and reduce smoking. This study will consist of a local cross sectional pilotstudy including 100 asymptomatic FH patients recruited from the lipid clinic at Odense University Hospital and hereafter a regional cross-sectional on approximately 600 asymptomatic FH patients in the Region of Southern Denmark recruited from the lipid clinics trough the national patient registry. In the pilot study, patients will undergo lipid analysis and non-contrast / contrast CT for description of coronary arterial calcium, and plaque morphology in this patient group. This will provide knowledge for planning the regional cross sectional study describing subclinical atherosclerosis in this population. Patients will furthermore be randomized to see their coronary CT scan or not. Mean LDL-C change and smoking status will be evaluated one year after. The benefit of finding subclinical atherosclerotic disease with the possibility to improve lipid-lowering treatment for prevention of future premature ischemic heart disease is considered to outweigh the minor radiation exposure in this trial. If LDL-C is reduced significantly and smoking reduction is significant trough a simple intervention as showing the CT scan to the patient, this study can provide knowledge whether CT screening of this patient group should be considered in Denmark.

Conditions

Familial Hypercholesterolemia; Atherosclerosis

Keywords

Familial Hypercholesterolemia; Subclinical Coronary Atherosclerosis; Coronary computerized tomography; Coronary arterial calcium score; Screening; Risc stratification

Outcome Measures

Primary Outcomes (7)

• Coronary arterial calcium score (CACS)

  Mean CACS of the population

  18 months

• CACS

  Median CACS of the population

  18 months

• Plaque composition

  proportion of soft and calcified plaques

  18 months

• Plaque volume (mean)

  Mean size of plaques described in mm.

  18 months

• Plaque volume (median)

  Median size of plaques described in mm.

  18 months

• Severity of stenosis (number of stenosis)

  Percentage of vessel lumen compromised by plaque described as number of minor, moderate and severe stenosis.

  18 months

• Severity of stenosis (proportion of stenosis)

  Percentage of vessel lumen compromised by plaque described as proportion of minor, moderate and severe stenosis.

  18 months

Secondary Outcomes (4)

• Change in LDL-C levels.

  12 months

• Change in smoking status

  12 months

• Change in mean consumption cigarettes per day

  12 months

• Prevalence of femoral and carotid plaques

  18 months

Study Arms (2)

Coronary CT scan visualized for patient

EXPERIMENTAL

The patient is allowed to see the CT image of his/hers coronary vessels, including oral describtion of the findings.

Behavioral: Visualization of coronary Imaging and oral description

Coronary CT scan NOT visualized for patient

NO INTERVENTION

The patient is not allowed to see the CT image of his/hers coronary vessels.

Interventions

Visualization of coronary Imaging and oral description BEHAVIORAL

The participants is allowed to see their coronary CT scan including oral description. The study will test the effect on smoking habit and changes in LDL-C in one year.

Coronary CT scan visualized for patient

Eligibility Criteria

• Age: 20 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with genetically or clinically FH (DLCN score \> 6) between the age of 20 and 70 are eligible patients in DANFOCOS.

You may not qualify if:

• History of ASCVD defined as myocardialinfarction, procedural revascularisation, CABG and/or objective evidence if ischaemia (exercise stress test, stress echocardiography, myocardial perfusion scintigraphy, stress cardiac magnetic resonance, coronary angiography, cardiac CT), angina pectoris, ischaemic stroke or a medically (aspirin, clopidogrel, persantin) treated transitory ischaemic attack, and symptomatic peripheral vascular disease with ankle-brachial index below 0.9 or procedural revascularisation.
• Current Pregnancy or planning pregnancy (due to radiation issues)
• eGFR \< 60 ml/min/1,73 m2 (due to CT-contrast)
• Prior allergic reaction to CT-contrast.
• PCSK9-inhibitor treatment
• Life expectancy \< 5 years.
• Secondary dyslipidemia
• Dysregulated diabetes
• Dysregulated hypothyreosis TSH \> 4,0 IU/L.
• Combined hyperlipidemia: TG \> 4 mmol/L
• Nefrotic syndrome: proteinuria \> 3 g/L and s-albumin \< 30 g/l
• History of primary billiary cirrhosis
• Low-carb-high-fat diet.
• Pharmacological induced dyslipidemia
• Three vessels disease

Sponsors & Collaborators

• Odense University Hospital: lead

Study Sites (1)

Odense University Hospital

Odense, 5000, Denmark

Location

Related Publications (18)

• Levenson AE, de Ferranti SD. Familial Hypercholesterolemia. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, et al., editors. Endotext. South Dartmouth (MA)2000

  BACKGROUND

• Bundgaard H SMea. Regionernes klinisk kvalitetsdatabase. Familiær hyperkolesterolæmi databasen. 2020 [Available from: https://www.rkkp.dk/kvalitetsdatabaser/databaser/databasen-for-familiaer-hyperkolesterolaemi/

  BACKGROUND

• Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS, Wiklund O, Hegele RA, Raal FJ, Defesche JC, Wiegman A, Santos RD, Watts GF, Parhofer KG, Hovingh GK, Kovanen PT, Boileau C, Averna M, Boren J, Bruckert E, Catapano AL, Kuivenhoven JA, Pajukanta P, Ray K, Stalenhoef AF, Stroes E, Taskinen MR, Tybjaerg-Hansen A; European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013 Dec;34(45):3478-90a. doi: 10.1093/eurheartj/eht273. Epub 2013 Aug 15.

  PMID: 23956253 BACKGROUND

• Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, Chapman MJ, De Backer GG, Delgado V, Ference BA, Graham IM, Halliday A, Landmesser U, Mihaylova B, Pedersen TR, Riccardi G, Richter DJ, Sabatine MS, Taskinen MR, Tokgozoglu L, Wiklund O; ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020 Jan 1;41(1):111-188. doi: 10.1093/eurheartj/ehz455. No abstract available.

  PMID: 31504418 BACKGROUND

• Rosso A, Pitini E, D'Andrea E, Massimi A, De Vito C, Marzuillo C, Villari P. The Cost-effectiveness of Genetic Screening for Familial Hypercholesterolemia: a Systematic Review. Ann Ig. 2017 Sep-Oct;29(5):464-480. doi: 10.7416/ai.2017.2178.

  PMID: 28715059 BACKGROUND

• Sturm AC, Knowles JW, Gidding SS, Ahmad ZS, Ahmed CD, Ballantyne CM, Baum SJ, Bourbon M, Carrie A, Cuchel M, de Ferranti SD, Defesche JC, Freiberger T, Hershberger RE, Hovingh GK, Karayan L, Kastelein JJP, Kindt I, Lane SR, Leigh SE, Linton MF, Mata P, Neal WA, Nordestgaard BG, Santos RD, Harada-Shiba M, Sijbrands EJ, Stitziel NO, Yamashita S, Wilemon KA, Ledbetter DH, Rader DJ; Convened by the Familial Hypercholesterolemia Foundation. Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel. J Am Coll Cardiol. 2018 Aug 7;72(6):662-680. doi: 10.1016/j.jacc.2018.05.044.

  PMID: 30071997 BACKGROUND

• Nicholls SJ, Puri R, Anderson T, Ballantyne CM, Cho L, Kastelein JJ, Koenig W, Somaratne R, Kassahun H, Yang J, Wasserman SM, Scott R, Ungi I, Podolec J, Ophuis AO, Cornel JH, Borgman M, Brennan DM, Nissen SE. Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: The GLAGOV Randomized Clinical Trial. JAMA. 2016 Dec 13;316(22):2373-2384. doi: 10.1001/jama.2016.16951.

  PMID: 27846344 BACKGROUND

• Raal FJ, Hovingh GK, Catapano AL. Familial hypercholesterolemia treatments: Guidelines and new therapies. Atherosclerosis. 2018 Oct;277:483-492. doi: 10.1016/j.atherosclerosis.2018.06.859.

  PMID: 30270089 BACKGROUND

• Hedegaard BS. A danish nationwide study og individuals suspected of FH referred from general practice to lipid clinics: Clinical characteristics, plasma lpipoprotein(A) and final diagnosis. Atherosclerosis. 2021.

  BACKGROUND

• Schmidt EB, Hedegaard BS, Retterstol K. Familial hypercholesterolaemia: history, diagnosis, screening, management and challenges. Heart. 2020 Dec;106(24):1940-1946. doi: 10.1136/heartjnl-2019-316276. Epub 2020 Sep 15. No abstract available.

  PMID: 32933999 BACKGROUND

• Perez de Isla L, Alonso R, Muniz-Grijalvo O, Diaz-Diaz JL, Zambon D, Miramontes JP, Fuentes F, Gomez de Diego JJ, Gonzalez-Estrada A, Mata N, Saltijeral A, Barreiro M, Tomas M, de Andres R, Argueso R, Serrano Gotarredona MP, Navarro Herrero S, Perea Palazon RJ, de Caralt TM, Suarez de Centi LA, Zhilina S, Espejo Perez S, Padro T, Mata P; SAFEHEART investigators. Coronary computed tomographic angiography findings and their therapeutic implications in asymptomatic patients with familial hypercholesterolemia. Lessons from the SAFEHEART study. J Clin Lipidol. 2018 Jul-Aug;12(4):948-957. doi: 10.1016/j.jacl.2018.04.003. Epub 2018 Apr 17.

  PMID: 29753733 BACKGROUND

• Luirink IK, Kuipers IM, Hutten BA, Planken RN, Backx APCM, Groothoff JW, Wiegman A. Coronary computed tomography angiography and echocardiography in children with homozygous familial hypercholesterolemia. Atherosclerosis. 2019 Jun;285:87-92. doi: 10.1016/j.atherosclerosis.2019.04.219. Epub 2019 Apr 11.

  PMID: 31048103 BACKGROUND

• Lindholt JS, Sogaard R, Rasmussen LM, Mejldal A, Lambrechtsen J, Steffensen FH, Frost L, Egstrup K, Urbonaviciene G, Busk M, Diederichsen ACP. Five-Year Outcomes of the Danish Cardiovascular Screening (DANCAVAS) Trial. N Engl J Med. 2022 Oct 13;387(15):1385-1394. doi: 10.1056/NEJMoa2208681. Epub 2022 Aug 27.

  PMID: 36027560 BACKGROUND

• Jensen JM, Gerdes LU, Jensen HK, Christiansen TM, Brorholt-Petersen JU, Faergeman O. Association of coronary heart disease with age-adjusted aortocoronary calcification in patients with familial hypercholesterolaemia. J Intern Med. 2000 Apr;247(4):479-84. doi: 10.1046/j.1365-2796.2000.00630.x.

  PMID: 10792562 BACKGROUND

• Wang W, Yang L, Wang S, Wang Q, Xu L. An automated quantification method for the Agatston coronary artery calcium score on coronary computed tomography angiography. Quant Imaging Med Surg. 2022 Mar;12(3):1787-1799. doi: 10.21037/qims-21-775.

  PMID: 35284280 BACKGROUND

• Romanens M, Mortensen MB, Sudano I, Szucs T, Adams A. Extensive carotid atherosclerosis and the diagnostic accuracy of coronary risk calculators. Prev Med Rep. 2017 Mar 14;6:182-186. doi: 10.1016/j.pmedr.2017.03.006. eCollection 2017 Jun.

  PMID: 28352516 BACKGROUND

• Preston DL, Ron E, Tokuoka S, Funamoto S, Nishi N, Soda M, Mabuchi K, Kodama K. Solid cancer incidence in atomic bomb survivors: 1958-1998. Radiat Res. 2007 Jul;168(1):1-64. doi: 10.1667/RR0763.1.

  PMID: 17722996 BACKGROUND

• Einstein AJ, Knuuti J. Cardiac imaging: does radiation matter? Eur Heart J. 2012 Mar;33(5):573-8. doi: 10.1093/eurheartj/ehr281. Epub 2011 Aug 9.

  PMID: 21828062 BACKGROUND

MeSH Terms

Conditions

Hyperlipoproteinemia Type II; Atherosclerosis

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Finn Lund Henriksen, PhD

  Odense University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomised controlled trial

Study Record Dates

• First Submitted: February 1, 2023
• First Posted: March 7, 2023
• Study Start: September 1, 2023
• Primary Completion: May 30, 2025
• Study Completion: May 30, 2025
• Last Updated: April 15, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)